This chapter shows how the field of neuroprogression and staging has evident conceptual and historical connections with past clinical and research efforts made in Europe during the first half of the nineteenth century. ‘Psychiatrie’ was a new branch of medicine trying to find and define disorders within the psychic, symptomatic, and behavioural realms. Disorders, and boundaries between them, were still largely unknown, as well as the course of clinical presentation. As early as 1850, theory and research pointed to some unifying perspectives with characteristic ‘evolving deterioration in transformation’. Some classical descriptions of ‘stages’ and ‘phases’ of disease bear clear resemblance to current staging models. ‘Phrenalgie’ and ‘Seelenschmerz’, for example, correspond essentially to the current definitions of ‘initial vulnerability’ or ‘increased risk’. Relating severity of presentation and intensity of recurrence to bad prognosis became clear and opened empirical ways to understand pathophysiology, reframed nowadays under the ideas of neuroprogression and staging.